Cardiovascular diseases are the leading cause of mortality in developed countries. Atherosclerosis, defined as the buildup of lipid rich plaques within the vascular intima, is the foremost pathology underlying these conditions. This process initiates with accumulation of oxidized low density lipoproteins (oxLDL) within the vessel walls, triggering monocyte recruitment, diapedesis and differentiation to macrophages, which subsequently uptake oxLDL via scavenger receptors. This unregulated uptake of oxLDL leads to formation of foam cells and secretion of inflammatory mediators (Yoshimoto et al., Advances in experimental medicine and biology 2002, 507, 403-7). The atherogenic accumulation of lipid laden macrophages results in plaques that can exhibit the clinical endpoints of myocardial infarction, stroke or peripheral arterial disease. Traditional therapies to reduce vascular lipid burden focus on lowering the hepatic synthesis of cholesterol, however, these therapies fail to target lesion development.
Accordingly, new agents and methods for treating atherosclerosis are needed.